The European patent application EP 92 114 942 suggests an improved fibrin glue for surgical wound application or treatment of hemophilics. This fibrin glue contains a high amount of aprotinin which is the preferred protease inhibitor according to EP 92 114 942. Further there is suggested the use of snake venom derived proteolytic enzymes, preferably the compound batroxobin. It is advantageous to apply such a fibrin glue in order to treat also people having developed immunogenic reactions against thrombin with a fibrin glue
The European patent application 92 112 295 suggests a fibrin glue which comprises additionally ingredients for culturing embryonic cells of mammals in one or both of the components A and B of the fibrin glue. Also this specific fibrin glue for in vitro fertilization contains aprotinin as preferred clinically accepted protease inhibitor.
EP-0 339 607 A2 is concerned with a composition for repair of cartilage and bone and method for their preparation as skeletal tissue implant. For this purpose the implantation of cells expressing a chondrocyte phenotype (80.times.10.sup.6 cells/ml), namely bone marrow derived chondrocytes or osteoblasts of autologous or homologous origin or homologous committed chondrocytes or autologous or homologous muscle fibroblast derived chondrocytes or any other progenital cells from mesenchymal origin is used. These cells are embedded in a biodegradable, biocompatible, biological resorbable immobilization vehicle (BRIV) adhesive glue consisting of fibrinogen, thrombin, CaCl.sub.2, protease inhibitor, and at least 10%, preferably 15-30%, serum. As suitable protease inhibitors epsilon-aminocaproic acid and tranexamic acid are mentioned.
WO-A-92/22312 is concerned with a tissue treatment composition, especially an adhesive composition comprising fibrin or fibrinogen and a biodegradable and biocompatible polymer capable of forming a viscous aqueous solution. In addition to glueing, the tissue adhesive composition may be used for slow-release of a drug incorporated into it or for anti-adherence purposes, for wound healding, etc. One of these polymers is identified as the proteoglycan hyaluronic acid.
GB-A-2 102 811 deals with a tissue adhesive and a method of producing the same. The adhesive contains factor VIII, fibrinogen and an antibiotic.
WO-A-86/01814 discloses a fibrin adhesive prepared as a concentrate from single donor fresh frozen plasma. It does not deal with pool plasma fractions.
WO-A-92/15341 is dealing with an adhesive for bonding biological tissue in particular human body tissue. The adhesive contains fibrinogen, a substance capable of supplying calcium ions, blood-coagulating factor XIIIa and, as a fibrinogen-splitting substance, a snake-venom enzyme.
EP-A-0 166 263 discloses a filler composition for filling in defect or hollow portion of bone and kit or set for the preparation of the filler composition. The filler composition comprises fibrin and a calcium phosphate compound.
DE-A-22 01 993 discloses an enzyme preparation and a process for production of the same. The enzyme disclosed is a protease having thrombolytic activity and has been isolated from the snake venom of the snake bothrops.
Aprotinin is a quite common protease inhibitor. Chemically this compound is a polypeptide of 58 amino acids and is predominantly prepared from mammalian origin like bovine organs. Aprotinin is occuring in pankreatic, lung, liver, spleen cells. It inhibits plasmin, trypsin, chymotrypsin and other kininogenases. In therapy it is used to treat severe bleeding or treatment of shock.
However, also aprotinin may be immunogenic. Moreover, since most of the aprotinin is of bovine origin and some virus contamination has been reported further use of aprotinin is not entirely harmless.
The fibrin clot formed by the fibrin glues of prior art often dries out during ageing and turns into a hard and knife-sharp clot which may injure tissue if in motion.